A regional interdisciplinary center will be established with the main emphasis on relating fundamental research on muscle to the problems of cardiovascular disease. Proteins from the normal myocardium and from hearts involed in cardiomyopathies will be characterized and their properties related to the myofibrillar proteins of skeletal muscle and other motile systems. Fine structural studies of filament organization in cardiac, in skeletal and in vascular smooth muscle, will be related to biochemical studies on the contractile proteins. Energetics of myocardial, smooth and striated muscle contraction will be further characterized and related to the basic mechanism of contraction. The metabolism and function of the sarcoplasmic reticulum and mitochondria will be investigated in normal and ischemic hearts. The mechanism of excitation-contraction coupling and drug action in cardiac and vascular smooth muscle will be explored. Cardiac and vascular smooth muscle morphogenesis will be characterized and the involvement of the latter in atherosclerosis will be determined. Single cell electrophysiological studies of cardiac muscle will be related to the role of the sympathetic-adrenal axis in cardiac arrhythmias. Methods to be employed include conventional and intermediate voltage transmission electron microscopy, scanning electron microscopy, electron probe x-ray microanalysis, x-ray diffraction, tissue culture, radioisotope flux, analytical ultracentrifuge, fast reaction kinetic techniques and voltage clamping, in addition to standard biochemical and physiological methods.